Cancer is a serious and debilitating disease brought on by abnormal and unchecked cell division in a patient. Current treatment strategies include chemotherapy, radiation therapy, and surgery. These treatment options may be singular treatments or combined for a more effective regimen. Unfortunately, many patients do not respond well to current chemotherapeutic regimens or develop resistance after prolonged treatment. In addition, for many chemotherapeutics, there is a maximal lifetime level of drug that a patient may be administered. In this case, new drugs must be tried. Thus, there is a need for development of new and varied chemotherapeutic compounds to assist in the treatment of cancer.
An important aspect of cancer, as opposed to infection caused by an exogenous pathogen for example, is that the disease is caused by cells already existing in the patient. These cells are similar in many ways to healthy tissue and reside among healthy cells in the patient. Thus, chemotherapeutic compounds, even if directly administered to a tumor, run the risk of entering and affecting healthy tissue in addition to cancerous tissue. This non-specific delivery can cause systemic and serious side effects in a patient including nausea, weakness, bleeding problems, infection, and hair loss. To avoid these systemic effects, chemotherapeutic compounds may be conjugated to a targeting molecule that assists with the specific and direct delivery of a chemotherapeutic compound to cancerous tissue only, preventing delivery to healthy tissue. These drugs may be associated with fewer and less severe side effects than traditional therapy, and so there is a need to develop chemotherapeutics that are effective in isolation, but are also suitable for conjugation to a targeting molecule.
Various types of agents have been described for use in treatment of cancer. Many of these compounds pose challenges. For instance, many compounds described for use in treatment of cancer have problems associated with toxicity. Some compounds present challenges related to their chemical synthesis. There are also challenges associated with finding appropriate permutations of therapeutic agents for combination therapy. Furthermore, only a minority of agents identified for use in treatment of cancer are suitable for conjugation to a targeting moiety. Accordingly, there remains a need for new compounds and conjugates for use in treatment of cancer.